AP Biology 2007-2008
Chapter 12: The Cell Cycle:
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Function of Cell Division
making new cells
growth
repair & renew
continuity of life
asexual reproduction
amoeba
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Cell division / Asexual reproduction
Mitosis
produce cells with same information
identical daughter cells
exact copies
clones
same amount of DNA
same number of chromosomes
same genetic information
Aaaargh!
I’m seeing double!
2005-2006
Asexual reproduction
• All prokaryotes reproduce asexually
• Single celled eukaryotes
– yeast
– Paramecium – Amoeba
• Simple multicellular eukaryotes reproduce asexually
– Hydra
• budding
What are the disadvantages of asexual reproduction?
What are the advantages?
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Budding in Yeast
Binary fission in Amoeba
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nuclear pores
nuclear pore
nuclear envelope nucleolus
histone protein
chromosome DNA
Function
protects DNA
Structure
nuclear envelope
double membrane
membrane fused in spots to create pores
allows large macromolecules to pass through
Nucleus
What kind of molecules need to
pass through?
Cytoskeleton
• microfilaments, intermediate filaments, microtubules microtubules
Chromosomes movement in cell division
microfilament
Cell division, cleavage furrow formation
Centrioles
• Found in animal cells only
• organize microtubules and form spindle fiber.
Spindle itself is made of microtubules
• guide chromosomes in mitosis
Cross section of a centriole 9+2 arrangement
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Getting the right stuff
What is passed on to daughter cells?
exact copy of genetic material = DNA
mitosis
division of organelles & cytoplasm
cytokinesis
chromosomes (stained orange) in kangaroo rat epithelial cell
notice cytoskeleton fibers
includes
is divided into is divided into
Concept Map
Section 10-2
Cell Cycle
M phase (Mitosis) Interphase
G1 phase S phase G2 phase Prophase Metaphase Anaphase Telophase
Cytokinesis
End Show
10-2 Cell Division
Slide 12 of 38
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Cell Cycle
Events of the Cell Cycle
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Overview of mitosis
interphase prophase (pro-metaphase)
metaphase anaphase telophase
cytokinesis
I.P.M.A.T.
DNA packing
The double helix of DNA is highly negatively charged due to all the negatively charged
phosphates in the backbone.
Histones are positively charged proteins that
wrap up DNA through interactions between their positive charges and negative charges of DNA.
Double-stranded DNA loops around 8 histones twice,
forming the nucleosome,
which is the building block of chromatin packaging.
DNA Packing
DNA is packaged by forming coils of nucleosomes, called chromatin fibers. These fibers are condensed
into chromosomes during mitosis, or the process of cell division.
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Copying DNA & packaging it…
After DNA duplication, chromatin condenses
coiling & folding to make a smaller package
DNA
chromatin
mitotic chromosome
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double-stranded mitotic human chromosomes
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Mitotic Chromosome
Duplicated chromosome
2 sister chromatids
narrow at centromeres
contain identical
copies of original DNA
single-stranded
double-stranded
• Kinetochores are protein complexes associated with centromeres
• In animal cells, assembly of spindle microtubules begins in the centrosome, the microtubule
organizing center
• An aster (a radial array of short microtubules) extends from each centrosome
• The spindle includes the centrosomes, the microtubules, and the asters
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Interphase
90% of cell life cycle
cell doing its “everyday job”
• Divided into 3 phases:
– G1 = 1st Gap
• cell grows
– S = DNA Synthesis
– G2 = 2nd Gap
Prepare for mitosis
G0
Interphase
• Nucleus well-defined
– DNA loosely packed in long chromatin fibers
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G1 Phase
•the cell
– increases in size
– synthesizes new proteins and organelles
Copyright Pearson Prentice Hall
S Phase
• chromosomes are replicated by DNA synthesis
• The centrosome replicates forming two centrosomes that migrate to opposite ends of the cell during
prophase and prometaphase
–Once a cell enters the S phase, it usually completes the rest of the cell cycle.
End Show
10-2 Cell Division
Slide 25 of 38
Events of the Cell Cycle
The G2 Phase (Second Gap Phase)
Organelles, proteins, molecules, and membrane required for cell division
Once G2 is complete, the cell is ready to start the M phase—Mitosis
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Mitosis
Dividing cell’s DNA between 2 daughter nuclei
“dance of the chromosomes”
4 phases
prophase
metaphase
anaphase
telophase
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Prophase
Chromatin condenses
visible chromosomes
chromatids
Centrioles move to opposite poles of cell
Protein fibers cross cell to form mitotic spindle
microtubules coordinates movement of chromosomes
Nucleolus disappears
Nuclear membrane breaks down
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Transition to Metaphase
Prometaphase
spindle fibers (microtubules) attach to centromeres at
kinetochores
chromosomes begin moving
Metaphase
Chromosomes align along middle of cell
– metaphase plate - the imaginary midway point between two spindle poles.
• meta = middle
Centrioles migrate to
opposite poles in the cell, riding along on the
developing spindle.
Nonkinetochore
microtubules (or polar Micortubules) from
opposite poles overlap each other extensively during metaphase.
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spindle fibers coordinate movement and helps to ensure chromosomes separate properly so each new nucleus receives only 1 copy of each chromosome
Anaphase
Separation of chromatids
• In anaphase, proteins holding together sister chromatids are inactivated
– Sister chromatids separate at kinetochores to become individual chromosomes
2 chromosomes 1 chromosome
2 chromatids
single-stranded double-stranded
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Anaphase
Sister chromatids move to opposite poles
pulled at centromeres
pulled apart by motor proteins interacting with kinetochore microtubules
• Centromeres move toward the poles as the
microtubules that connect them shorten. This
shortening is due to the
removal of tubulin subunits from the kinetochore ends (+ end) of the microtubules.
Chromosome movement
• During anaphase region of overlap is reduced as motor proteins attached to the microtubules walk them away from one another using ATP.
• As microtubules push themselves apart from each other, their spindle poles are pushed apart, elongating the cell.
• At the same time, the microtubules continue to overlap by the addition of tubulin subunits to their overlapping ends.
Cell Elongation by Nonkinetochore (Polar) Microtubules
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Telophase
Chromosomes arrive at opposite poles
daughter nuclei form
nucleoli form
chromosomes disperse
no longer visible under light microscope
Spindle fibers disperse
Cytokinesis begins
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Cytokinesis in animals
cleavage furrow forms by constriction belt of actin microfilaments around equator of cell
splits cell in two
like tightening a draw string
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Cytokinesis in Animals
(play Cells Alive movies here) (play Thinkwell movies here)
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Mitosis in whitefish blastula
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Mitosis in animal cells
Cytokinesis in Plants
Cell plate forms
• vesicles derived from Golgi line up at equator
• vesicles fuse to form 2 cell membranes
new cell wall laid down between membranes
– new cell wall fuses with existing cell wall
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Cytokinesis in plant cell
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Mitosis in plant cell
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onion root tip
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Overview of mitosis
interphase prophase (pro-metaphase)
metaphase anaphase telophase
cytokinesis
I.P.M.A.T.
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G2
S G1
M metaphase prophase
anaphase telophase
interphase (G1, S, G2 phases) mitosis (M)
cytokinesis (C) C
Frequency of cell division varies by cell type
embryo
cell cycle < 20 minute
skin cells
divide frequently throughout life
12-24 hours cycle
liver cells
retain ability to divide, but keep it in reserve
divide once every year or two
mature nerve cells & muscle cells
do not divide at all after maturity
permanently in G0
Frequency of cell division
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Overview of Cell Cycle Control
Two irreversible points in cell cycle
replication of genetic material
separation of sister chromatids
Checkpoints
process is assessed & possibly halted
centromere
sister chromatids
single-stranded
chromosomes double-stranded chromosomes
There’s no turning back,
now!
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Checkpoint control system
3 major checkpoints:
G1 Phase checkpoint
can DNA synthesis begin?
G2 Phase checkpoint
has DNA synthesis been completed correctly?
commitment to mitosis
M phase checkpoint
are all chromosomes attached to spindle?
can sister chromatids separate correctly?
• For many cells, the G1 checkpoint seems to be the most important
• If a cell receives a go-ahead signal at the G1
checkpoint, it will usually complete the S, G2, and M phases and divide
• If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing
state called the G0 phase
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Cell cycle
M Mitosis
G1 Gap 1
G0 Resting G2
Gap 2
S Synthesis
Cell has a “life cycle”
cell is formed from a mitotic division
cell grows & matures to divide again
cell grows & matures to never divide again
G1, S, G2, M G1G0
epithelial cells, blood cells,
stem cells
brain / nerve cells muscle cells liver cells
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G0 phase
M Mitosis
G1 Gap 1
G0 Resting G2
Gap 2
S Synthesis
G0 phase
non-dividing, differentiated state
most human cells in G0 phase
liver cells
in G0, but can be
“called back” to cell
cycle by external cues
nerve & muscle cells
highly specialized
arrested in G0 & can never divide
The Cell Cycle Clock: Cyclins and Cyclin- Dependent Kinases
• Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks)
• Cdks activity fluctuates during the cell cycle because it is controled by cyclins, so named because their concentrations vary with the cell cycle
• MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers a cell’s passage past the G2 checkpoint into the M phase
© 2011 Pearson Education, Inc.
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Cell cycle signals
Cell cycle controls
cyclins
regulatory proteins
levels cycle in the cell
Cdk’s
cyclin-dependent kinases
phosphorylates cellular proteins
activates or inactivates proteins
Cdk-cyclin complex
triggers passage through different stages of cell cycle
Figure 12.17
(a) Fluctuation of MPF activity and cyclin concentration during the cell cycle
(b) Molecular mechanisms that help regulate the cell cycle MPF activity
Cyclin
concentration
Time
M G1 S G2 M G1 S G2 M G1
Cdk Degraded
cyclin
Cyclin is degraded
MPF G2
checkpoint Cdk
Cyclin
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During Anaphase, MPF switches itself off by starting a process that leads to destruction of cyclin molecules.
Without cyclin molecules Cdk
molecules become inactive, bringing mitosis to a close.
How does cell stop cell division?
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Cyclin & Cyclin-dependent kinases
CDKs & cyclin drive cell from one phase to next in cell cycle
proper regulation of cell cycle is so key to life that the genes for these regulatory proteins
have been highly conserved through evolution
the genes are basically the same in yeast,
insects, plants &
animals (including humans)
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External signals
Growth factors
coordination between cells
protein signals released by
body cells that stimulate other cells to divide
density-dependent inhibition
crowded cells stop dividing
each cell binds a bit of growth factor
not enough activator left to trigger division in any one cell
anchorage dependence
to divide cells must be attached to a substrate
“touch sensor” receptors
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E2F
nucleus
cytoplasm
cell division
nuclear membrane
growth factor
protein kinase cascade
nuclear pore
chromosome
cell surface Cdk
receptor
P
P P
P P
Growth factor signals
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Example of a Growth Factor
Platelet Derived Growth Factor (PDGF)
made by platelets in blood clots
binding of PDGF to cell receptors stimulates cell division in fibroblast (connective tissue)
heal wounds
Don’t forget to mention erythropoietin!
(EPO)
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Growth Factors and Cancer
Growth factors can create cancers
proto-oncogenes
normal growth factor genes that become oncogenes (cancer-causing) when mutated
stimulates cell growth
if oncogenes are turned “ON” can cause cancer
example: RAS (activates cyclins)
tumor-suppressor genes
inhibits cell division
if switched “OFF” can cause cancer
example: p53
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DNA damage is caused by heat, radiation, or chemicals.
p53 allows cells with repaired DNA to divide.
Step 1
DNA damage is caused by heat, radiation, or chemicals.
Step 1 Step 2
Damaged cells continue to divide.
If other damage accumulates, the cell can turn cancerous.
Step 3
p53 triggers the destruction of cells damaged beyond repair.
ABNORMAL p53 NORMAL p53
abnormal p53 protein
cancer cell
Step 3
The p53 protein fails to stop cell division and repair DNA.
Cell divides without repair to damaged DNA.
Cell division stops, and p53 triggers enzymes to repair damaged region.
Step 2
DNA repair enzyme p53
protein
p53 protein
p53 — master regulator gene
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Development of Cancer
Cancer develops only after a cell experiences
~6 key mutations (“hits”)
unlimited growth
turn on growth promoter genes
ignore checkpoints
turn off tumor suppressor genes (p53)
escape apoptosis
turn off suicide genes
immortality = unlimited divisions
turn on chromosome maintenance genes
promotes blood vessel growth
turn on blood vessel growth genes
overcome anchor & density dependence
turn off touch-sensor gene
It’s like an out of control
car!
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What causes these “hits”?
Mutations in cells can be triggered by
UV radiation
chemical exposure
radiation exposure
heat
cigarette smoke
pollution
age
genetics
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Tumors
Mass of abnormal cells
Benign tumor
abnormal cells remain at original site as a lump
p53 has halted cell divisions
most do not cause serious problems &
can be removed by surgery
Malignant tumors
cells leave original site
lose attachment to nearby cells
carried by blood & lymph system to other tissues and start more tumors = metastasis
impair functions of organs throughout body
The Evolution of Mitosis
• Since prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission
• Certain protists exhibit types of cell division that seem intermediate between binary fission and mitosis
© 2011 Pearson Education, Inc.
Figure 12.13
(a) Bacteria
(b) Dinoflagellates
(d) Most eukaryotes
Intact nuclear envelope
Chromosomes Microtubules
Intact nuclear envelope
Kinetochore microtubule
Kinetochore microtubule
Fragments of
nuclear envelope Bacterial
chromosome
(c) Diatoms and some yeasts